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We report on a comprehensive study of the systemic RNAi-response in the desert locust, Schistocerca gregaria. Upon intra-abdominal injection of dsRNA for two housekeeping genes (alpha-tubulin la and gapdh) in the range of pg amounts of dsRNA per mg tissue, a potent reduction of their corresponding mRNA was obtained. Moreover, the observed transcript knockdown significantly increased in at least a 10 days period and eventually resulted in high mortality upon silencing of the alpha-tubulin 1a gene. A more moderate RNAi-response was however observed in the reproductive systems. Analysis of the tissue-dependent transcript level profile of several putative RNAi-genes indicated reduced levels of two genes, namely sg-dicer-2 and sg-argonaute-2, in the reproductive systems. By silencing these components, we confirmed their importance in the RNAi-process and suggest that their expression levels are determinant for tissue-dependent differences in the potency of RNAi in the desert locust. (C) 2012 Elsevier Ltd. All rights reserved.